PROJECT SUMMARY/ABSTRACT The developmental origins of psychopathology can be traced to in utero experiences. However, there is limited research into prenatal and newborn markers of early psychiatric problems. A promising line of inquiry suggests that exposure to maternal distress during pregnancy can have a lasting effect on child health and disease susceptibility. However, mechanisms associating maternal risk factors with child outcomes remain poorly understood. Emotion dysregulation (ED) is a transdiagnostic vulnerability factor that underlies many devastating and costly psychiatric diagnoses, including personality disorders, anxiety, depression, and suicide risk. Therefore, ED serves as a viable index of complex psychopathology among adults. In children, early signs of ED likely precede formal psychiatric diagnoses, such as anxiety, attention deficit/hyperactivity disorder, and difficulties with impulse or temper regulation. However, there have been few studies examining intergenerational transmission of ED or ED trajectories among mothers and their young children from an innovative Research Domain Criteria (RDoC) perspective. The objective of this proposal is to advance current understanding of ED across generations by (1) enrolling pregnant women with the full range of emotional distress, and (2) examining promising clinical and developmental indices of risk for psychopathology in their children. By adding to an existing, NIMH-funded cohort, the proposed study will follow N=324 mother-child dyads from pregnancy through 18 months, a developmental stage when child behavior problems begin to show rank- order stability. Consistent with the RDoC perspective, mothers will be recruited to meet a uniform distribution of ED scores and will complete a comprehensive prenatal laboratory battery to assess behavioral, psychophysiological, and self-reported measures of ED, stress, and psychopathology. Fetal physiological responses will also be recorded prenatally, as early indices of risk for ED. Within 24 hours of birth, babies will undergo a reliable and valid newborn neurobehavioral exam designed to detect emerging signs of dysregulation (e.g., high arousal and low self-regulation). At 7- and 18-months, mother-child pairs will return to the laboratory to engage in dyadic tasks that reliably elicit co-regulation and/or dysregulation. Behavioral and psychophysiological response patterns will be assessed in mother and child using dynamical systems methods that are appropriate for capturing complex developmental processes. This innovative and rigorously designed study unites a complex clinical sample with a well-established developmental design and advanced statistical approaches to better understand early mental health trajectories. When the aims of this project are realized, we will have an improved understanding of ED in mothers and their children during a critical stage that lays the building blocks for later health, development, and wellbeing. This longitudinal study will lay a foundation for research continuing into childhood and will advance a programmatic line of inquiry devoted to understanding dysregulated women and children to improve early intervention and prevent psychopathology.